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Identification
HMDB Protein ID HMDBP08781
Secondary Accession Numbers
  • 14504
Name Diphosphoinositol polyphosphate phosphohydrolase 1
Synonyms
  1. DIPP-1
  2. Diadenosine 5',5'''-P1,P6-hexaphosphate hydrolase 1
  3. Nucleoside diphosphate-linked moiety X motif 3
  4. Nudix motif 3
Gene Name NUDT3
Protein Type Unknown
Biological Properties
General Function Involved in hydrolase activity
Specific Function Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. InsP6 (inositol hexakisphophate) is not a substrate. Acts as a negative regulator of the ERK1/2 pathway. Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with Ap6A and Ap5A being the preferred substrates. The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A. Also able to hydrolyze 5-phosphoribose 1-diphosphate.
Pathways
  • Inositol Phosphate Metabolism
Reactions
Diphospho-myo-inositol polyphosphate + Water → myo-inositol polyphosphate + Phosphoric acid details
GO Classification
Biological Process
cell-cell signaling
diadenosine polyphosphate catabolic process
diphosphoinositol polyphosphate catabolic process
Cellular Component
cytoplasm
Function
catalytic activity
hydrolase activity
Molecular Function
diphosphoinositol-polyphosphate diphosphatase activity
inositol diphosphate tetrakisphosphate diphosphatase activity
inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 1-diphosphatase activity
inositol-1,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity
inositol-1-diphosphate-2,3,4,5,6-pentakisphosphate diphosphatase activity
inositol-3,5-bisdiphosphate-2,3,4,6-tetrakisphosphate 5-diphosphatase activity
inositol-3-diphosphate-1,2,4,5,6-pentakisphosphate diphosphatase activity
inositol-5-diphosphate-1,2,3,4,6-pentakisphosphate diphosphatase activity
magnesium ion binding
Cellular Location
  1. Cytoplasm (Probable)
Gene Properties
Chromosome Location 6
Locus 6p21.2
SNPs NUDT3
Gene Sequence
>519 bp
ATGATGAAGCTCAAGTCGAACCAGACCCGCACCTACGACGGCGACGGCTACAAGAAGCGG
GCCGCATGCCTGTGTTTCCGCAGCGAGAGCGAGGAGGAGGTGCTACTCGTGAGCAGTAGT
CGCCATCCAGACAGATGGATTGTCCCTGGAGGAGGCATGGAGCCCGAGGAGGAGCCAAGT
GTGGCAGCAGTTCGTGAAGTCTGTGAGGAGGCTGGAGTAAAAGGGACATTGGGAAGATTA
GTTGGAATTTTTGAGAACCAGGAGAGGAAGCACAGGACGTATGTCTATGTGCTCATTGTC
ACTGAAGTGCTGGAAGACTGGGAAGATTCAGTTAACATTGGAAGGAAGAGGGAATGGTTT
AAAATAGAAGACGCCATAAAAGTGCTGCAGTATCACAAACCCGTGCAGGCATCATATTTT
GAAACATTGAGGCAAGGCTACTCAGCCAACAATGGCACCCCAGTCGTGGCCACCACATAC
TCGGTTTCTGCTCAGAGCTCGATGTCAGGCATCAGATGA
Protein Properties
Number of Residues 172
Molecular Weight 19470.855
Theoretical pI 6.345
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Diphosphoinositol polyphosphate phosphohydrolase 1
MMKLKSNQTRTYDGDGYKKRAACLCFRSESEEEVLLVSSSRHPDRWIVPGGGMEPEEEPS
VAAVREVCEEAGVKGTLGRLVGIFENQERKHRTYVYVLIVTEVLEDWEDSVNIGRKREWF
KIEDAIKVLQYHKPVQASYFETLRQGYSANNGTPVVATTYSVSAQSSMSGIR
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O95989
UniProtKB/Swiss-Prot Entry Name NUDT3_HUMAN
PDB IDs
GenBank Gene ID AF062529
GeneCard ID NUDT3
GenAtlas ID NUDT3
HGNC ID HGNC:8050
References
General References
  1. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed:14574404 ]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  4. Fisher DI, Safrany ST, Strike P, McLennan AG, Cartwright JL: Nudix hydrolases that degrade dinucleoside and diphosphoinositol polyphosphates also have 5-phosphoribosyl 1-pyrophosphate (PRPP) pyrophosphatase activity that generates the glycolytic activator ribose 1,5-bisphosphate. J Biol Chem. 2002 Dec 6;277(49):47313-7. Epub 2002 Oct 4. [PubMed:12370170 ]
  5. Safrany ST, Caffrey JJ, Yang X, Bembenek ME, Moyer MB, Burkhart WA, Shears SB: A novel context for the 'MutT' module, a guardian of cell integrity, in a diphosphoinositol polyphosphate phosphohydrolase. EMBO J. 1998 Nov 16;17(22):6599-607. [PubMed:9822604 ]
  6. Safrany ST, Ingram SW, Cartwright JL, Falck JR, McLennan AG, Barnes LD, Shears SB: The diadenosine hexaphosphate hydrolases from Schizosaccharomyces pombe and Saccharomyces cerevisiae are homologues of the human diphosphoinositol polyphosphate phosphohydrolase. Overlapping substrate specificities in a MutT-type protein. J Biol Chem. 1999 Jul 30;274(31):21735-40. [PubMed:10419486 ]
  7. Yang X, Safrany ST, Shears SB: Site-directed mutagenesis of diphosphoinositol polyphosphate phosphohydrolase, a dual specificity NUDT enzyme that attacks diadenosine polyphosphates and diphosphoinositol polyphosphates. J Biol Chem. 1999 Dec 10;274(50):35434-40. [PubMed:10585413 ]
  8. Thorsell AG, Persson C, Graslund S, Hammarstrom M, Busam RD, Hallberg BM: Crystal structure of human diphosphoinositol phosphatase 1. Proteins. 2009 Oct;77(1):242-6. doi: 10.1002/prot.22489. [PubMed:19585659 ]